Recently released H1N1 sequences have significantly accelerated
pandemic concerns. These sequences have receptor changes on the
H1N1 virus which produce a case fatality rate at or near 100% in
many countries.

These receptor binding domain changes are on multiple backgrounds,
but the transmission and expansion of these fatal sequences in eastern
Europe, including Russia, have increased concerns, as has the "low
reactor" status as determined by sequences from the Ukraine
pneumonic flu virus.

When reports from Ukraine described a high
number of fatal cases associated with lung destruction and
a hemorrhagic component, involvement of D225G and D225N receptor
changes on the virus was predicted. However, although WHO had
sent a team to Ukraine and had sent representative clinical samples
to the CDC and WHO regional labs, the WHO characterized the sequence
changes in the Ukraine as insignificant.

The association of D225G and D225N was more directly supported
by sequences from the United States, Mexico, and Sweden, which
identified samples with both D225G and D225N. Thus, once again
two different changes were appended onto the same genetic background
at a given location, but the background varied from location to
location, supporting recombination. Moreover, in Mexico there
were fatal infections with D225G and D225N. Both were in San Luis
Potosi and collected with a day of each other, supporting transmission.

However, although the above data left little dount that the receptor
binding changes were transmitting and jumping from one genetic
background to the other via recombination, the WHO working hypothesis
held that each of these changes was independent and due to copy
errors within each patient.

This position had no support from the data. The changes at position
225 were only found in 1% of sequences, but were in six of six
fatal cases in Ukraine. Similarly, isolates with both changes
were found in two patients at the same location at the same time
in Mexico. The WHO working hypothesis was yet another attempt
to explain genetic drift by random mutation, even though the existing
data offered no support for such a claim.

The recent data demonstrates a case fatality rate at or near 100%
in multiple countries, with clustering of polymorphisms and patients
consistent with transmission and recombination. Moreover, Mill
Hill in London ran an antigenicity test on one of the Ukraine
samples and found it to be a low reactor, raising concerns that
changes at position 225 will become more common in the next H1N1
wave, which could have catastrophic consequences, while WHO is
trying to construct a defense for its outdated random mutations
as an explanation of genetic drift and viral evolution.

The transmission of a deadly H1N1, coupled with a WHO wedded
to an outdated paradigm, significantly increases pandemic concerns.